Direct effect of nicotine on mesolimbic dopamine release in rat nucleus accumbens shell
Direct effect of nicotine on mesolimbic dopamine release in rat nucleus accumbens shell
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DOI：
10.1016/j.neulet.2011.02.035
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发表时间：
2011-04-08
影响因子：
2.5
通讯作者：
Westerink, B. H. C.
中科院分区：
文献类型：
--
作者：
Kleijn, J.;Folgering, J. H. A.;Westerink, B. H. C.
尼古丁通过腹侧被盖区（VTA）的体树突部位的局部作用刺激多巴胺（DA）细胞放电，增加丘脑核（NAcc）中DA的释放。此外，尼古丁还可通过直接作用于NAcc来调节DA释放。本研究通过全身应用尼古丁以及在大鼠的VTA和NAcc壳区域局部应用尼古丁来检查后一种机制对NAcc DA释放的贡献。此外，静脉注射尼古丁对腹侧被盖区多巴胺能神经元的细胞放电率的影响进行了测量。全身给予尼古丁（0.32 mg/kg s.c.）NAcc中的细胞外DA水平增加至基线的1.5倍，而VTA中的DA水平保持不受影响。在局部NAcc输注尼古丁（1 μ M和10 μ M）后观察到类似的DA增加。然而，VTA中需要10-1000倍的尼古丁浓度才能使同侧NAcc中的细胞外DA水平增加150%。此外，电生理学实验表明，多巴胺放电率在腹侧被盖区显示出增加的趋势后，尼古丁剂量为0.1毫克/公斤静脉注射。总之，这些数据表明，尼古丁对DA释放的影响，在水平的NAcc可能是更重要的奖励效果比原来提出的。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Nicotine stimulates dopamine (DA) cell firing via a local action at somatodendritic sites in the ventral tegmental area (VTA), increasing DA release in the nucleus accumbens (NAcc). Additionally, nicotine may also modulate DA release via a direct effect in the NAcc. This study examined the contribution of the latter mechanism on NAcc DA release by applying nicotine systemically, as well as locally in the VTA and NAcc shell region in rats. Furthermore, the effect of i.v. nicotine on cell firing rate of dopaminergic neurons in the VTA was measured. Systemic administration of nicotine (0.32 mg/kg s.c.) increased extracellular DA levels in the NAcc to similar to 1.5 fold of baseline, while DA levels in the VTA remained unaffected. A similar DA increase was observed after local NAcc infusion of nicotine (1 mu M and 10 mu M). However, 10-1000-fold higher nicotine concentrations were required in the VTA to produce a comparable 150% increase in extracellular DA levels in the ipsilateral NAcc. Additionally, electrophysiological experiments showed that the dopaminergic firing rate in the VTA showed a trend towards an increase after a nicotine dose of 0.1 mg/kg i.v. Taken together these data indicate that the effects of nicotine on DA release at the level of the NAcc might be more important for the rewarding effects than originally proposed. (C) 2011 Elsevier Ireland Ltd. All rights reserved.